We propose to continue and significantly extend the research we began in 2010, with support from the National Cancer Institute, to develop a system that improves the capture of patient-reported as well as objectively measured data from patients in cancer clinical trials. The system, CYCORE (CYberinfrastructure for COmparative effectiveness REsearch), is a robust software-based prototype for a user-friendly, cyberinfrastructure (CI) that supports the acquisition, storage, visualization, analysis, and sharing of data important for cancer-related comparative effectiveness research (CER). Our initial project began with the intent to solve the problem of how to collect data on patients enrolled in cancer clinical trials that would improve the ability of cancer researchers to gather patient-reported data on such things as symptoms, quality of life, performance status and physiological parameters that signal how well participants are doing with their treatment. We have developed an initial, highly successful prototype of CYCORE, tested it in several use- cases, and now have a small but highly enthusiastic community of users. What we propose herein is based both on our assessment of critical needs for scalability and extensibility of the system as well as on user input about what they find useful in CYCORE and what features they would like to see in subsequent versions. Hence, we endeavor to position CYCORE uniquely to support a rapidly growing interest in cancer-related CER. Our vision for CYCORE is to support an expanded community of researchers in a variety of research settings. In this project, we focus on the following Aims: Aim 1: Improve scalability and performance: Exploit the emerging trends in service-oriented architectures, virtualization, and cloud computing to scale our infrastructure to accommodate both existing and emerging sensors, processing, analysis and reporting tools. Aim 2: Expand capability for new sensors and address fault tolerance and self-healing. Develop and test the acquisition of data from new sensors, while increasing the system's reliability. Aim 3: Introduce a new cancer control use case for CYCORE Aim 4: Incorporate new algorithms that support the detection and analysis of outcomes important in cancer CER. Provide a generic infrastructure for algorithm definition and execution and implement some of the algorithms needed for the pilot trials (e.g., dehydration, performance status, movement, and smoking cessation). Aim 5: Improve security, privacy and data sharing capabilities of CYCORE - optimize how CYCORE handles issues related to data security, anonymization, and confidentiality in order to facilitate data sharing. Integrate with external systems to ingest data into CYCORE and also to export data for sharing with other researchers. Aim 6: Develop and Implement a model for sustainability - develop a sustainability model for CYCORE to ensure support for programming, project and outreach staff in the future. Aim 7: Expand and enrich the community of CYCORE users. Expand, support and nurture the community of CYCORE users.